Adding Lp(a) to ApoB improves aortic-stenosis risk prediction, especially in men, UK Biobank cohort of 365,771 (Eur J Prev Cardiol 2026)

Original title: Moving beyond Low-Density Lipoprotein cholesterol: apolipoprotein B and Lipoprotein (a) for sex-specific risk assessment of aortic stenosis in the UK Biobank

Eur J Prev Cardiol · 8 May 2026 · 8

Shi W, Han H, Pei J, Ding C, Yao Y, Zhang H, Xu H, Wu Y, Li Z, Zhang B

UK Biobank analysis of 365,771 participants (mean age 56.1±8.07, 55.74% female) free of baseline cardiovascular disease, examining sex-specific associations between a comprehensive lipid profile and incident aortic stenosis (AS) and regurgitation (AR). Hierarchical clustering identified an apoB-containing cluster and an apoA-containing cluster, with Lp(a) occupying an independent branch. Over a median 13.8 years (3118 AS, 1239 AR events), total cholesterol, apoB, LDL-C, non-HDL-cholesterol and Lp(a) were each independently associated with higher AS risk in both sexes (all p<0.01), with Lp(a) showing an additional sex-specific effect (p for interaction=0.004). ApoB outperformed LDL-C for AS association, and adding Lp(a) to either marker improved AS risk prediction, especially in men; no lipid trait was associated with AR. The authors propose apoB replace LDL-C as the primary particle-burden marker, with Lp(a) added as an independent sex-specific risk enhancer for AS.

Original abstract

Background And Aims: Lipid abnormalities-particularly low-density lipoprotein cholesterol (LDL-c) and lipoprotein(a) [Lp(a)]-have been implicated in aortic stenosis (AS), yet translation into clinically actionable risk assessment remains underdeveloped, especially regarding sex-specific evaluation. This study aims to quantify sex-specific associations between a comprehensive lipid profile and the risks of AS and aortic regurgitation (AR), and to identify the most informative markers and marker combinations for improved risk assessment.

Methods: In 365,771 UK Biobank participants (mean age 56.1±8.07 years; 55.74% female) free of baseline cardiovascular disease. Routine lipid traits underwent hierarchical clustering and were related to incident AS and AR using sex-stratified Cox models. Discordance analyses and time-dependent concordance index were employed to compare risk assessment performance of different markers.

Results: Hierarchical clustering revealed three clusters in both sexes-an apolipoprotein B (apoB)-containing cluster and an apolipoprotein A containing cluster-while Lp(a) occupied an independent branch. During a median follow-up of 13.8 years, there were 3118 incident AS and 1239 AR cases. Total cholesterol, apoB, LDL-c, non-high-density lipoprotein cholesterol in apoB-containing cluster and Lp(a) were each independently associated with higher AS risk in both sexes (all P < 0.01), with Lp(a) conferred additional sex-specific effect (P for interaction = 0.004). Discordance analyses showed that apoB outperformed LDL-c in association with AS. Addition of Lp(a) to ApoB or LDL-c improved AS risk prediction over either marker alone-especially in men. No lipid trait was associated with AR.

Conclusion: ApoB may substitute for LDL-c as the primary particle-burden marker, whereas Lp(a) should be incorporated as an independent sex-specific risk enhancer in AS risk assessment. These results support sex-specific, multi-biomarker assessment to optimize AS risk stratification and future preventive strategies.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.